The indefinite survival of human corneal transplants and cultured mouse thyroid and pancreas allografts gives credence to the hypothesis that any normal tissue which is completely freed of blood elements (capillaries and leucocytes) may be unable to induce allograft rejection. Endocrine tissue is particularly relevant to this hypothesis because it can function in small pieces fed by diffusion after being freed of its capillary bed. The ability to produce large numbers of cultured grafts that survive indefinitely in allogeneic recipients makes it feasible now to perform experiments to determine the cell types required for graft rejection and their specificity. This is especially important today since the ability to clone T-cells in vitro is advancing rapidly. The mechanism of acquired tolerance of cultured grafts should also be determinable by presently available techniques. Thus, this research is potentially important to both the treatment of human disease and the advancement of basic immunological knowledge. Objectives: A. Improve the method of culturing thyroid grafts to (1) reduce time of culture, (2) reduce damage to endocrine tissue and (3) increase reproducibility of long term acceptance in allogeneic recipients; B. Use the cultured thyroid model to answer the following questions: (1) Are Lyt-2 cells required for graft rejection? (2) Will anti-Ia serum increase the percent of long term survivors in cultured allografts? (3) What is the mechanism of the development of acquired tolerance to cultured allografts? Subsequent experiments will depend on the answers obtained to these questions. If the answer to question 1 is yes, then we will determine if the injection of CTL depleted of strongly positive Lyt-1 cells can cause graft rejection. If the answer to question 1 is no, then the production of DH with killed cells will have a high priority. These experiments should be done eventually in any case. If the anti-Ia serum improves the long term survival of cultured allografts, then the application of this technology to pancreas transplants would have a high priority. If anti-Ia serum fails to improve cultured allograft survival then the explanation of acquired tolerance becomes more important. Hopefully any information obtained in the last set of experiments will be applicable to the improvement of allograft survival.